Pathogenesis of Fabry nephropathy: description of key players in fibrosis

ROZENFELD, P.; BOLLA, MARÍA DE LOS ÁNGELES; QUIETO, PEDRO; PISANI, A; FERIOZZI, S; NEUMAN, PABLO; BONDAR, C.

Simposio; WORLDSymposium Lysosomal Disease Network; 2020

Kidney is one of the main target organs inFabry disease. Renal involvement is characterized by proteinuria andprogressive chronic kidney disease leading to end-stage renal disease.Pathogenic mechanisms in the progression of renal damage in Fabry disease arenot thoroughly known yet. The lysosomal Gb3 deposition is the first step ofcomplex pathological pathways resulting in renal sclerosis/fibrosis. Ourhypothesis is that Fabry disease associated cellular alterations in tubularcells induce the production of TGF-β1, the main profibrotic cytokine. The aimof this work was to study the mechanisms leading to fibrosis in kidney fromhuman Fabry patients. Fifteen renal biopsies from naïve Fabry patients wereincluded in this work and histological and immunohistochemical analysis wascarried out. Our findings showed positive staining for TGF-β1 in tubularepithelial cells in biopsies from Fabry patients. In addition, apoptosis was assessedby active caspase 3 staining and expression was detected in tubular andmesangial glomerular cells. We also performed a study for α-SMA, amyofibroblast´s marker, and its expression was revealed on pericytessurrounding peritubular capillaries, smooth muscle cells of blood vessels,mesangial cells and periglomerular zone. In conclusion our results show for thefirst time that TGF-β1 is expressed in human renal tissue from Fabry patients,and that this profibrotic cytokine is mainly produced by proximal tubularcells. In addition both, peritubular interstitium and glomeruli, presentedcells positive for myofibroblasts markers.